This research proposal is designed to delineate the metabolic interrelationships of glucose and fatty acid metabolism in skeletal muscle and to determine the influence of extracellular VLDL-triglyceride on glucose utilization in muscle and adipose tissue. In addition to the effects of exercise and experimental diabetes mellitus on the metabolism of glucose, free fatty acids and VLDL-triglyceride will be studied. Much of the planned research will make use of a new experimental technique, the isolated perfused rat hindquarter which will permit skeletal muscle to be studied in an in vitro system which closely simulates the in vivo situation. By use of this general approach it is hoped that further insight will be gained into the complex interrelationships of the various fuels which provide metabolic energy to peripheral tissues in both physiologic and pathologic circumstances and to determine the mechanism by which the frequent co-existence of hypertriglyceridemia and hyperglycemia observed in both diabetic and hyperlipemic patients can be explained.